FUNGAL INFECTION

Aspergillosis

Opportunistic infections caused by Aspergillus sp and inhaled as mold conidia, leading to hyphal growth and invasion of blood vessels, hemorrhagic necrosis, infarction, and potential dissemination to other sites in susceptible patients.

Symptoms and Signs: Noninvasive or, rarely, minimally locally invasive colonization of preexisting cavitary pulmonary lesions also may occur in the form of fungus ball (aspergilloma) formation or chronic progressive aspergillosis.

Primary superficial invasive aspergillosis is uncommon but may occur in burns, beneath occlusive dressings, after corneal trauma (keratitis), or in the sinuses, nose, or ear canal.

Invasive pulmonary aspergillosis usually extends rapidly, causing progressive, ultimately fatal respiratory failure unless treated promptly and aggressively. A. fumigatus is the most common causative species.

 Extrapulmonary disseminated aspergillosis may involve the liver, kidneys, brain, or other tissues and is usually fatal. Primary invasive aspergillosis may also begin as an invasive sinusitis, usually caused by A. flavus, presenting as fever with rhinitis and headache

Bronchiectasis 
- Bronchiectasis is abnormal and irreversible dilatation of the bronchi and bronchioles (greater than 2 mm in diameter) secondary to inflammatory weakening of bronchial wall.
- Occur in childhood and early adult life
- Persistent cough with copious amount of foul smelling purulent sputum

Aetiopathogenesis
Bronchial wall destruction is due to:
- Endobronchial obstruction due to foreign body
- Infection due to local obstruction or impaired defence mechanism 

Clinical conditions:
- Hereditary and congenital factors
- Obstruction
- Secondary complication

Hereditary and congenital factors:
- Congenital bronchiectasis due to developmental defects
- Cystic fibrosis causing defective secretion resulting in obstruction
- Hereditary immune defiency diseases
- Immotile cilia syndrome- immotile cilia of respiratory tract, sperms causing Kartagener’s syndrome (bronchiectasis, situs inversus and sinusitis) and male infertility
- Allergic bronchial asthma patients

Obstruction:

Localised variety in one part of bronchial system.
Obstruction can be due to
Foreign body
Endobronchial tumors
Hilar lymph nodes
Inflammatory scarring (TB)

Secondary complication:

Necrotizing pneumonia in Staph infection and TB

Morphologic changes

- Affects distal bronchi and bronchioles
- Lower lobes more frequently
- Lungs involved diffusely/segmentally
- Left lower lobe than right
- Pleura fibrotic & thickened adherent to chest wall

C/S lung: Honey-combed appearance

Microscopic examination:
Bronchiole-dilated
Bronchial epithelium-normal, ulcerated, squamous metaplasia
Bronchial wall-infiltration by ac & Ch inflammatory cells,
destruction of muscle, elastic tissue 
Lung parenchyma-fibrosis, surrounding tissue pneumonia
Pleura-fibrotic and adherent

Human immunodeficiency virus (HIV)
1. Part of the Retroviridae family (i.e., it is a retrovirus).
2. Basic virion structure
a. The nucleocapsid contains single stranded RNA and three enzymes: reverse transcriptase, integrase, and protease.

b. An exterior consists of two glycoproteins, gp120 and gp41, which are imbedded in the lipid bilayer. This lipid bilayer was obtained from the host cell via budding.

3. Virion characteristics

a. The HIV genome includes:

(1) gag gene—codes for core proteins.
(2) pol gene—codes for its three enzymes.
(3) env gene—codes for its two envelope glycoproteins.

b. HIV enzymes

(1) Reverse transcriptase—reverse transcription of RNA to viral DNA.
(2) Integrase—responsible for integrating viral DNA into host DNA.
(3) Protease—responsible for cleaving precursor proteins. 

4. Pathogenicity

a. HIV mainly infects CD4 lymphocytes, or helper T cells. Its envelope protein, gp120, binds specifically with CD4 surface
receptors. After entry, viral RNA is transcribed by reverse transcriptase to viral DNA and integrated into  the host DNA. New virions are synthesized and released by lysis of the host cell.

b. The predominant site of HIV replication is lymphoid tissues.
c. Although HIV mainly infects CD4 helper T cells, it can bind to any cell with a CD4 receptor, including macrophages, monocytes, lymph node dendritic cells, and a selected number of nerve cells. Macrophages are the first cells infected by HIV.

5. HIV infection versus acquired immunodeficiency syndrome (AIDS).

a. AIDS describes an HIV-infected person who has one of the following conditions:

(1) A CD4 lymphocyte count of less than 200.
(2) The person is infected with an opportunistic infection or other AIDS-defining illness, including (but not limited to) tuberculosis, recurrent pneumonia infections, or invasive cervical cancer.
b. The cause of death in an AIDS patient is most likely due to an opportunistic infection.

6. Common opportunistic infections associated with AIDS:
a. Pneumonia caused by Pneumocystis jiroveci (carinii). 
b. Tuberculosis.
c. Periodontal disease—severe gingivitis, periodontitis, ANUG, necrotizing stomatitis.
d. Candidiasis.
e. Oral hairy leukoplakia (EBV).
f. Kaposi’s sarcoma (HHV-8).
g. Recurrent VZV infections.
h. Condyloma acuminatum or verruca vulgaris (warts, HPV)—less common.
i. CMV infections.
j. Disseminated herpes simplex, herpes zoster.
k. Hodgkin’s, non-Hodgkin’s lymphoma.

7. Laboratory diagnosis of HIV

a. ELISA test—detects HIV antibodies.
False negatives do occur.

b. Western blot—detects HIV proteins.
There is a 99% accuracy rate when both the ELISA test and Western blot are used to diagnose HIV infection.
c. PCR—more sensitive; can amplify and identify the virus at an early stage.

8. Treatment
a. Inhibitors of reverse transcriptase.

(1) Nucleoside analogs
(a) Inhibit viral replication via competitive inhibition.
(b) Examples: zidovudine (AZT), didanosine, lami- vudine, stavudine.

(2) Nonnucleoside inhibitors.
(a) Act by binding directly to reverse transcriptase.
(b) Examples: nevirapine, delavirdine.
b. Protease inhibitor.
c. “Triple cocktail” therapy—often consists of two nucleoside inhibitors and a protease inhibitor.

Nephrolithiasis, urolithiasis

Formation of calculi (calcium stones) in the kidney (nephrolithiasis) or urinary tract (urolithiasis).
Commonly associated with hyperparathyroidism.
Signs and symptoms 

urinary tract obstruction, severe pain, and pyelonephritis.

Note: an enlarged prostate can also cause urinary tract obstruction in males.

HERPES SIMPLEX

An infection with herpes simplex virus characterized by one or many clusters of small vesicles filled with clear fluid on slightly raised inflammatory bases.

The two types of herpes simplex virus (HSV) are HSV-1 and HSV-2. HSV-1 commonly causes herpes labialis, herpetic stomatitis, and keratitis; HSV-2 usually causes genital herpes, is transmitted primarily by direct (usually sexual) contact with lesions, and results in skin lesions

Primary infection of HSV-1 typically causes a gingivostomatitis, which is most common in infants and young children. Symptoms include irritability, anorexia, fever, gingival inflammation, and painful ulcers of the mouth.

Primary infection of HSV-2 typically occurs on the vulva and vagina or penis in young adults

Herpetic whitlow, a swollen, painful, and erythematous lesion of the distal phalanx, results from inoculation of HSV through a cutaneous break or abrasion and is most common in health care workers.

Bacterial meningitis (pyogenic, suppurative infections)

1. Common causes include:
a. Escherichia coli in newborns.
b. Haemophilus influenzae in infants and children.
c. Neisseria meningitides in young adults.
d. Streptococcus pneumoniae and Listeria monocytogenes in older adults.

Clinical findings include severe headache, irritability, fever, and a stiff neck.
a. A spinal tap shows CSF fluid that is cloudy or purulent and is under increased pressure. There is also an increase in protein and a decrease in glucose levels.
3. Can be fatal if left untreated.